The basic amino acid transporter of the blood-brain barrier was identified and shown to be homologous to the cell surface receptor for ecotropic murine retroviruses. Transporter mRNA expression was greatest in brain capillaries and exceeded that in parenchymal brain by >10 fold. The structural selectivity of the cerebrovascular large neutral amino acid carrier was characterized and used to design drugs showing rapid transport into brain. One such drug, D,L-NAM, was shown to have the highest affinity of any known agent for the transporter and to be taken up into brain 20 times more rapidly than its clinical analogue, melphalan. The pharmacokinetics of beta-N-methylamino-L-alanine (BMAA), a neurotoxin that has been implicated in the pathogenesis of amyotrophic lateral sclerosis and parkinsonism dementia in the western Pacific, was examined in rats. BMAA was found to reach toxic concentrations in brain following high dose administration and was transported into brain by the large neutral amino acid carrier of the blood-brain barrier. Saturable carriers were identified at the blood-brain barrier for manganese, calcium and chloride. The brain uptake and deposition of toxic metals, including aluminum, lead, cadmium and manganese, was enhanced by calcium deficiency, stressing the importance of diet in brain metal toxicity. Low dietary calcium also produced a precipitous drop (>90%) in serum copper and created imbalances in other essential brain metals.